PharmPK Discussion - 14C In Vivo Studies

On 13 Feb 2000 at 21:38:42, Richard.Knapp.aaa.aventis.com sent the message

Hello to all:

I am anticipating a request to perform an in vivo ADME study using a14C-labeled drug. I am interested in literature references/generalinformation sources on the design and conduct of such studies. Some obviousissues include estimation of the radiochemical dose (Ci of label to be givento a rat), safety (Is CO2 a problem?), sampling techniques (plasma, urine,feces) and pitfalls (effect of 14C label location on drug molecule, isotopeeffects etc.). Any help is welcome.

examine the structure oi the drug. is it likely to be cleaved or to haveadditonal molecules added? are there easily re,ovable methyl, mehtyl aminogroups prresetnt. can tou use deuterated compounds instead? these,with the newsoftware available in LC mass spec instruments PE biosystems can give very goodtraceability and compound identification wo concersn of duplication ofeffort/dup of staff/ prep room etc. they are not as sensitivie but. edoc

2. One of the best sources for monographs, bulletins and articles on thevarious aspects of conducting radiolabelled metabolism studies is the LSCmanufactures. Both Packard and Beckman have a history of highly usefuldocuments. And the older information is still part of current practice, sodon't be put off by a pre-1990 date. One example: "Liquid ScintillationAnalysis - Science and Technology", M. Kessler, ed, (1989) Packard Inst.Co., Meriden, CT